tbuckley/cabot-search huggingface dataset:
Risk of Mortality After a Diagnosis of Melanoma In Situ
Authors: Vishal R. Patel, Mya L. Roberson, Michael P. Pignone, Adewole S. Adamson
Journal: JAMA Dermatology (2023)

Importance The incidence of melanoma in situ (MIS) is increasing more rapidly than any invasive or in situ cancer in the US. Although more than half of melanomas diagnosed are MIS, information about long-term prognosis following a diagnosis of MIS remains unknown. Objective To evaluate mortality and factors associated with mortality after a diagnosis of MIS. Design, Setting, and Participants This population-based cohort study of adults with a diagnosis of first primary MIS from 2000 to 2018 included data from the US Surveillance, Epidemiology, and End Results Program, which were analyzed from July to September 2022. Main Outcomes and Measures Mortality after a diagnosis of MIS was evaluated using 15-year melanoma-specific survival, 15-year relative survival (ie, compared with similar individuals without MIS), and standardized mortality ratios (SMRs). Cox regression was used to estimate hazard ratios (HRs) for death by demographic and clinical characteristics. Results Among 137 872 patients with a first-and-only MIS, the mean (SD) age at diagnosis was 61.9 (16.5) years (64 027 women [46.4%]; 239 [0.2%] American Indian or Alaska Native, 606 [0.4%] Asian, 344 [0.2%] Black, 3348 [2.4%] Hispanic, and 133 335 [96.7%] White individuals). Mean (range) follow-up was 6.6 (0-18.9) years. The 15-year melanoma-specific survival was 98.4% (95% CI, 98.3%-98.5%), whereas the 15-year relative survival was 112.4% (95% CI, 112.0%-112.8%). The melanoma-specific SMR was 1.89 (95% CI, 1.77-2.02); however, the all-cause SMR was 0.68 (95% CI, 0.67-0.7). Risk of melanoma-specific mortality was higher for older patients (7.4% for those 80 years or older vs 1.4% for those aged 60-69 years; adjusted HR, 8.2; 95% CI, 6.7-10.0) and patients with acral lentiginous histology results (3.3% for acral lentiginous vs 0.9% for superficial spreading; HR, 5.3; 95% CI, 2.3-12.3). Of patients with primary MIS, 6751 (4.3%) experienced a second primary invasive melanoma and 11 628 (7.4%) experienced a second primary MIS. Compared with patients without a subsequent melanoma, the risk of melanoma-specific mortality was increased for those with a second primary invasive melanoma (adjusted HR, 4.1; 95% CI, 3.6-4.6) and was decreased for those with a second primary MIS (adjusted HR, 0.7; 95% CI, 0.6-0.9). Conclusions and relevance The results of this cohort study suggest that patients with a diagnosis of MIS have an increased but low risk of melanoma-specific mortality and live longer than people in the general population, suggesting that there is significant detection of low-risk disease among health-seeking individuals. Factors associated with death following MIS include older age (≥80 years) and subsequent primary invasive melanoma.
Preliminary Evidence for Genetic Nurture in Depression and Neuroticism Through Polygenic Scores
Authors: Justin D. Tubbs, Pak C. Sham
Journal: JAMA Psychiatry (2023)

Modeling genetic nurture (ie, the effects of parental genotypes through influences on the environment experienced by their children) is essential to accurately disentangle genetic and environmental influences on phenotypic variance. However, these influences are often ignored in both epidemiologic and genetic studies of depression.
Gut microbiota dysbiosis promotes the development of epithelial ovarian cancer <i>via</i> regulating Hedgehog signaling pathway
Authors: Xinyue Hu, Xuan Xu, Xiangdi Zeng, Rui Jin, Shengnan Wang, Huifu Jiang, Yuwen Tang, Guanxiang Chen, Jing Wei, Tingtao Chen, Qi Chen
Journal: Gut Microbes (2023)

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, which remains a threat to female health at all ages. Hypotheses for EOC development include the continuous presence of inflammation, in which microbiota and inflammatory cytokines participate in cancer-related signaling pathway activation. Hedgehog (Hh) signaling is prominent for EOC progression, and interacts with inflammation response related to gut microbiota (GM). However, the precise roles of GM during this process are unknown. Here, we showed that the GM from patients with EOC differed from that of healthy women and had GM dysbiosis. We found that EOC modeling may lead to GM changes in mice, and it restored after the administration of GM from healthy controls, while GM from patients with EOC further exacerbated GM dysbiosis. Furthermore, we found that GM from EOC markedly promoted tumor progression and activated Hh signaling; meanwhile, it increased the extent of inflammation and activated NF-κB signaling, but GM from healthy controls improved them. Our results demonstrate how GM dysbiosis promoted EOC progression by activating Hh signaling mediated by TLR4/NF-κB signaling. We anticipate our assay to be a new thought for exploring the role of GM in EOC development. Furthermore, improving GM dysbiosis is a novel therapeutic approach for delaying EOC development.
Comparison of Stroke Recurrence, Cardiovascular Events, and Death Among Patients With Pregnancy-Associated vs Non–Pregnancy-Associated Stroke
Authors: Yannick Béjot, Valérie Olié, Gregory Lailler, Clémence Grave, Nolwenn Regnault, Gauthier Duloquin, Jacques Blacher, Amélie Gabet
Journal: JAMA Network Open (2023)

Importance Women with pregnancy-associated stroke might have different risks of stroke recurrence, including during subsequent pregnancies, and other cardiovascular events due to pregnancy-specific stroke risk factors, such as gestational hypertension, preeclampsia, or gestational diabetes. Objective To estimate the rate of stroke recurrence, cardiovascular hospitalization, and death in women with pregnancy-associated stroke compared with women with non–pregnancy-associated stroke. Design, Setting, and Participants This cohort study included all women aged 15 to 49 years in France who were affiliated with the general scheme of French health care insurance (94% of women) and had a first hospitalization for stroke between January 1, 2010, and December 31, 2018. Women were followed up until December 31, 2020, with the registration of stroke recurrence, hospitalization for cardiovascular conditions, and death. Data were from the French health care database Système National des Données de Santé. Statistical analyses were conducted between December 2021 and September 2022. Exposure Pregnancy status at the time of stroke. Main Outcomes and Measures Poisson regressions were used to estimate incidence rates of these events with 95% CIs. We used Cox proportional hazards regression models to estimate the hazard ratios (HRs) of each event during the follow-up for women with a pregnancy-associated stroke vs women with a non–pregnancy-associated stroke. Results Among women aged between 15 and 49 years between 2010 and 2018 and living in France, 1204 had a pregnancy-associated stroke at a mean (SD) age of 31.5 (5.8) years, and 31 697 had a non–pregnancy-associated stroke at a mean age of 39.6 (8.2) years. Among the 1204 women with a pregnancy-associated stroke, the incidence rate was 11.4 (95% CI, 9.0-14.3) per 1000 person-years, with 2 recurrent events during a subsequent pregnancy. Compared with women with non–pregnancy-associated stroke, women with pregnancy-associated stroke had lower risks of ischemic stroke (adjusted HR, 0.53; 95% CI, 0.36-0.77), cardiovascular events (adjusted HR, 0.58; 95% CI, 0.49-0.69), and death (adjusted HR, 0.42; 95% CI, 0.22-0.79). In contrast, the risk of recurrent intracerebral hemorrhage and cerebral venous thrombosis did not differ significantly, whereas the risks of venous thromboembolism (HR, 2.02; 95% CI, 1.14-3.58) and acute coronary syndrome with ST-segment elevation (HR, 3.93; 95% CI, 1.10-14.0) were increased. Conclusions and Relevance In this cohort study, although the risks of ischemic stroke, overall cardiovascular events, and mortality were lower after a pregnancy-associated stroke than after a non–pregnancy-associated stroke, the risks of venous thromboembolism and acute coronary syndrome with ST-segment elevation were higher. Recurrent stroke during a subsequent pregnancy remained rare.
<i>N</i>‐Acetyl‐<scp>l</scp>‐cysteine‐Derived Carbonized Polymer Dots with ROS Scavenging via Keap1‐Nrf2 Pathway Regulate Alveolar Bone Homeostasis in Periodontitis
Authors: Xinchan Liu, Yubo Hou, Mingxi Yang, Xirui Xin, Yu Deng, Ruobing Fu, Xingchen Xiang, Niuben Cao, Xiaomeng Liu, Weixian Yu, Bai Yang, Yanmin Zhou
Journal: Advanced Healthcare Materials (2023)

Periodontitis is a type of chronic inflammatory oral disease characterized by the destruction of periodontal connective tissue and progressive alveolar bone resorption. As oxidative stress is the key cause of periodontitis in the early periodontal microenvironment, antioxidative therapy has been considered a viable treatment for periodontitis. However, more stable and effective reactive oxygen species (ROS)-scavenging nanomedicines are still highly needed due to the instability of traditional antioxidants. Herein, a new type of N-acetyl-l-cysteine (NAC)-derived red fluorescent carbonized polymer dots (CPDs) has been synthesized with excellent biocompatibility, which can serve as an extracellular antioxidant to scavenge ROS effectively. Moreover, NAC-CPDs can promote osteogenic differentiation in human periodontal ligament cells (hPDLCs) under H2 O2 stimulation. In addition, NAC-CPDs are capable of targeted accumulation in alveolar bone in vivo, reducing the level of alveolar bone resorption in periodontitis mice, as well as performing fluorescence imaging in vitro and in vivo. In terms of mechanism, NAC-CPDs may regulate redox homeostasis and promote bone formation in the periodontitis microenvironment by modulating the kelch-like ECH-associated protein l (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. This study provides a new strategy for the application of CPDs theranostic nanoplatform for periodontitis.
Use of Wearable Devices in Individuals With or at Risk for Cardiovascular Disease in the US, 2019 to 2020
Authors: Lovedeep S. Dhingra, Arya Aminorroaya, Evangelos K. Oikonomou, Arash Aghajani Nargesi, Francis Perry Wilson, Harlan M. Krumholz, Rohan Khera
Journal: JAMA Network Open (2023)

Importance Wearable devices may be able to improve cardiovascular health, but the current adoption of these devices could be skewed in ways that could exacerbate disparities. Objective To assess sociodemographic patterns of use of wearable devices among adults with or at risk for cardiovascular disease (CVD) in the US population in 2019 to 2020. Design, Setting, and Participants This population-based cross-sectional study included a nationally representative sample of the US adults from the Health Information National Trends Survey (HINTS). Data were analyzed from June 1 to November 15, 2022. Exposures Self-reported CVD (history of heart attack, angina, or congestive heart failure) and CVD risk factors (≥1 risk factor among hypertension, diabetes, obesity, or cigarette smoking). Main Outcomes and Measures Self-reported access to wearable devices, frequency of use, and willingness to share health data with clinicians (referred to as health care providers in the survey). Results Of the overall 9303 HINTS participants representing 247.3 million US adults (mean [SD] age, 48.8 [17.9] years; 51% [95% CI, 49%-53%] women), 933 (10.0%) representing 20.3 million US adults had CVD (mean [SD] age, 62.2 [17.0] years; 43% [95% CI, 37%-49%] women), and 5185 (55.7%) representing 134.9 million US adults were at risk for CVD (mean [SD] age, 51.4 [16.9] years; 43% [95% CI, 37%-49%] women). In nationally weighted assessments, an estimated 3.6 million US adults with CVD (18% [95% CI, 14%-23%]) and 34.5 million at risk for CVD (26% [95% CI, 24%-28%]) used wearable devices compared with an estimated 29% (95% CI, 27%-30%) of the overall US adult population. After accounting for differences in demographic characteristics, cardiovascular risk factor profile, and socioeconomic features, older age (odds ratio [OR], 0.35 [95% CI, 0.26-0.48]), lower educational attainment (OR, 0.35 [95% CI, 0.24-0.52]), and lower household income (OR, 0.42 [95% CI, 0.29-0.60]) were independently associated with lower use of wearable devices in US adults at risk for CVD. Among wearable device users, a smaller proportion of adults with CVD reported using wearable devices every day (38% [95% CI, 26%-50%]) compared with overall (49% [95% CI, 45%-53%]) and at-risk (48% [95% CI, 43%-53%]) populations. Among wearable device users, an estimated 83% (95% CI, 70%-92%) of US adults with CVD and 81% (95% CI, 76%-85%) at risk for CVD favored sharing wearable device data with their clinicians to improve care. Conclusions and Relevance Among individuals with or at risk for CVD, fewer than 1 in 4 use wearable devices, with only half of those reporting consistent daily use. As wearable devices emerge as tools that can improve cardiovascular health, the current use patterns could exacerbate disparities unless there are strategies to ensure equitable adoption.
The STAT1/HMGB1/NF-κB pathway in chronic inflammation and kidney injury after cisplatin exposure
Authors: Ying Fu, Yu Xiang, Ying Wang, Zhiwen Liu, Danyi Yang, Jie Zha, Chengyuan Tang, Juan Cai, Guochun Chen, Zheng Dong
Journal: Theranostics (2023)

Rationale: Cisplatin, a potent chemotherapeutic drug, induces side effects in normal tissues including the kidney.To reduce the side effects, repeated low-dose cisplatin (RLDC) is commonly used in clinical setting.While RLDC reduces acute nephrotoxicity to certain extents, a significant portion of patients later develop chronic kidney problems, underscoring the need for novel therapeutics to alleviate the long-term sequelae of RLDC therapy.Methods: In vivo, the role of HMGB1 was examined by testing HMGB1 neutralizing antibodies in RLDC mice.In vitro, the effects of HMGB1 knockdown on RLDC-induced nuclear factor-κB (NF-κB) activation and fibrotic phenotype changes were tested in proximal tubular cells.To study signal transducer and activator of transcription 1 (STAT1), siRNA knockdown and its pharmacological inhibitor Fludarabine were used.We also searched the Gene Expression Omnibus (GEO) database for transcriptional expression profiles and evaluated kidney biopsy samples from CKD patients to verify the STAT1/HMGB1/NF-κB signaling axis.Results: We found that RLDC induced kidney tubule damage, interstitial inflammation, and fibrosis in mice, accompanied by up-regulation of HMGB1.Blockage of HMGB1with neutralizing antibodies and Glycyrrhizin suppressed NF-κB activation and associated production of pro-inflammatory cytokines, reduced tubular injury and renal fibrosis, and improved renal function after RLDC treatment.Consistently, knockdown of HMGB1 decreased NF-κB activation and prevented the fibrotic phenotype in RLDC-treated renal tubular cells.At the upstream, knockdown of STAT1 suppressed HMGB1 transcription and cytoplasmic accumulation in renal tubular cells, suggesting a critical role of STAT1 in HMGB1 activation.Upregulation of STAT1/HMGB1/NF-κB along with inflammatory cytokines was also verified in kidney tissues of CKD patients.Conclusion: These results unravel the STAT1/HMGB1/NF-κB pathway that contributes to persistent inflammation and chronic kidney problems after cisplatin nephrotoxicity, suggesting new therapeutic targets for kidney protection in cancer patients receiving cisplatin chemotherapy.
Disparities in Suicide-Related Behaviors Across Sexual Orientations by Gender: A Retrospective Cohort Study Using Linked Health Administrative Data
Authors: Antony Chum, Chungah Kim, Andrew Nielsen, Gabriel John Dusing, Patricia O’Campo, Flora I. Matheson, Lucy Barker, Simone Vigod, Vicki Ling, Kinwah Fung, Sidney Kennedy
Journal: American Journal of Psychiatry (2023)

The authors used a population-representative sample and health administrative data to quantify suicide-related behavior leading to acute care or deaths across self-identified heterosexual, gay/lesbian, and bisexual individuals.Data from a population-based survey (N=123,995) were linked to health administrative data (2002-2019), and differences in time to suicide-related behavior events across sexual orientations were examined using Cox proportional hazards regression.The crude incidence rates of suicide-related behavior events per 100,000 person-years were 224.7 for heterosexuals, 664.7 for gay/lesbian individuals, and 5,911.9 for bisexual individuals. In fully adjusted (gender-combined) models, bisexual individuals were 2.98 times (95% CI=2.08-4.27) more likely to have an event, and gay men and lesbians 2.10 times (95% CI=1.18-3.71) more likely, compared with heterosexual individuals.In a large population-based sample of Ontario residents, using clinically relevant outcomes, the study found gay/lesbian and bisexual individuals to be at elevated risk of suicide-related behavior events. Increased education among psychiatric professionals is needed to improve awareness of and sensitivity to the elevated risk of suicide-related behavior among sexual minority individuals, and further research on interventions is needed to reduce such behaviors.
Dual-Targeted Gold Nanoprism for Recognition of Early Apoptosis, Dual-Model Imaging and Precise Cancer Photothermal Therapy: Erratum
Authors: Weiwei Zhang, Xiaoyuan Ding, Hao Cheng, Chenyang Yin, Jing Yan, Zhipeng Mou, Weiyun Wang, Danxi Cui, Cundong Fan, Dongdong Sun
Journal: Theranostics (2023)

[This corrects the article DOI: 10.7150/thno.34755.].
Fertility Trends and Adverse Pregnancy Outcomes in Female Patients With Psoriasis in the UK
Authors: Teng-Chou Chen, Ireny Y. K. Iskandar, Rosa Parisi, Matthias Pierce, Clare Tower, C. Elise Kleyn, Christopher E. M. Griffiths, Darren M. Ashcroft
Journal: JAMA Dermatology (2023)

Evidence regarding fertility trends and obstetric outcomes among patients with psoriasis is limited by studies of small sample sizes, noninclusion of comparators, and the lack of accurate pregnancy records.To investigate fertility rates and obstetric outcomes of pregnancies in female patients with psoriasis compared with age- and general practice-matched comparators without psoriasis.This population-based cohort study used data from 887 primary care practices that contributed to the UK Clinical Practice Research Datalink GOLD database between 1998 and 2019, linked to a pregnancy register and Hospital Episode Statistics. There were 6 223 298 patients of common childbearing ages (15-44 years), and 63 681 patients with psoriasis had at least 1 year of follow-up data prior to the diagnosis of psoriasis. For each patient with psoriasis, 5 patients were matched by age from the same general practice. The median follow-up duration was 4.1 years. Data analysis was performed in 2021.Patients with psoriasis were identified using clinical diagnostic codes from consultations.Fertility rates were calculated as the number of pregnancies per 100 patient-years. The outcomes of each pregnancy recorded in the pregnancy register or Hospital Episode Statistics were screened to identify obstetric outcomes. A negative binomial model was used to examine the association between psoriasis and the fertility rate. Logistic regression was applied to compare the association between psoriasis and obstetric outcomes.A total of 63 681 patients with psoriasis and 318 405 matched comparators were included in the analysis (median [IQR] age, 30 [22-37] years). Lower fertility rates (rate ratio, 0.75; 95% CI, 0.69-0.83) were found in patients with moderate to severe psoriasis. Compared with matched comparators without psoriasis, pregnancies in patients with psoriasis had a higher risk of loss (odds ratio, 1.06; 95% CI, 1.03-1.10); however, there was no increase in the risks of antenatal hemorrhage, preeclampsia, or gestational diabetes.In this cohort study, patients with moderate to severe psoriasis had a lower fertility rate, and the risk of pregnancy loss was higher than in matched comparators without psoriasis. Future research should identify the mechanism of increased risk of pregnancy loss among patients with psoriasis.
Fever, Pancytopenia, and Tender Erythematous Plaques in a Patient With Multiple Myeloma
Authors: Misako Yamaga, Sho Katayama, Mitsuhito Ota
Journal: JAMA Dermatology (2023)

A man in his late 60s who had received the first cycle of a chemotherapeutic regimen of ixazomib, lenalidomide, and dexamethasone for multiple myeloma presented to the dermatologic clinic with a 10-day history of fever and tender lesions on the neck and trunk. What is your diagnosis?
Comparative Venom Multiomics Reveal the Molecular Mechanisms Driving Adaptation to Diverse Predator–Prey Ecosystems in Closely Related Sea Snakes
Authors: Hao Zheng, Junjie Wang, Hairong Fan, Shuocun Wang, Ruiwei Ye, Linxue Li, Sheng Wang, An Li, Yiming Lu
Journal: Molecular Biology and Evolution (2023)

Abstract Predator–prey arms races are ideal models for studying the natural selection and adaptive evolution that drive the formation of biological diversity. For venomous snakes, venom is a key bridge linking snakes with their prey, but whether and how venom evolves under the selection of diet remains unclear. Here, we focused on two closely related sea snakes, Hydrophis cyanocinctus and Hydrophis curtus, which show significant differences in prey preferences. Data-independent acquisition (DIA)–based proteomic analysis revealed different degrees of homogeneity in the venom composition of the two snakes, which was consistent with the differential phylogenetic diversity of their prey. By investigating the sequences and structures of three-finger toxins (3FTx), a predominant toxin family in elapid venom, we identified significant differences between the two sea snakes in the binding activity of 3FTx to receptors from different prey populations, which could explain the trophic specialization of H. cyanocinctus. Furthermore, we performed integrated multiomic profiling of the transcriptomes, microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and proteomes of the venom glands; constructed venom-related mRNA–miRNA–lncRNA networks; and identified a series of noncoding RNAs involved in the regulation of toxin gene expression in the two species. These findings are highly informative for elucidating the molecular basis and regulatory mechanisms that account for discrepant venom evolution in response to divergent diets in closely related snakes, providing valuable evidence for the study of coselection and coevolution in predator–prey ecosystems.